Memantine in patients with frontotemporal lobar degeneration

A multicentre, randomised, double-blind, placebo-controlled trial

Adam L. Boxer, David S. Knopman, Daniel I. Kaufer, Murray Grossman, Chiadikaobi U Onyike, Neill Graf-Radford, Mario Mendez, Diana Kerwin, Alan Lerner, Chuang Kuo Wu, Mary Koestler, Jill Shapira, Kathryn Sullivan, Kristen Klepac, Kristine Lipowski, Jerin Ullah, Scott Fields, Joel H. Kramer, Jennifer Merrilees, John Neuhaus & 2 others M. Marsel Mesulam, Bruce L. Miller

Research output: Contribution to journalArticle

Abstract

Background: Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26-week open-label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the neuropsychiatric inventory (NPI). We aimed to determine whether memantine is an effective treatment for FTD. Methods: We did a randomised, parallel group, double-blind, placebo-controlled trial of 20 mg memantine taken orally daily for 26 weeks in patients with FTD. Participants met Neary criteria for behavioural variant FTD (bvFTD) or semantic dementia and had characteristic brain atrophy. Use of acetylcholinesterase inhibitors was prohibited. Individuals were randomly assigned to receive either memantine or matched placebo tablets (1:1) in blocks of two and four patients. All patients and study personnel were masked to treatment assignment. Primary endpoints were the change in total NPI score and clinical global impression of change (CGIC) score after 26 weeks and were analysed by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00545974. Findings: Of 100 patients screened, 81 were randomly assigned to receive memantine (39 patients) or placebo (42 patients). Five (6%) patients discontinued, and 76 completed the 26-week treatment. Enrolment numbers were lower than planned because of many patients' preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. Memantine treatment had no effect on either the NPI (mean difference 2·2, 95% CI -3·9 to 8·3, p=0·47) or CGIC (mean difference 0·0, -0·4 to 0·4, p=0·90) after 26 weeks of treatment. Memantine was generally well tolerated; however, patients in the memantine group had more frequent cognitive adverse events (six patients) than those in the placebo group (one). Interpretation: Memantine treatment showed no benefit in patients with FTD. These data do not support memantine use in FTD. Funding: Forest Research Institute.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalThe Lancet Neurology
Volume12
Issue number2
DOIs
StatePublished - Feb 2013

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Frontotemporal Lobar Degeneration
Memantine
Placebos
Cholinesterase Inhibitors
Equipment and Supplies
Therapeutics
Frontotemporal Dementia
Patient Preference
Tablets
Atrophy

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Memantine in patients with frontotemporal lobar degeneration : A multicentre, randomised, double-blind, placebo-controlled trial. / Boxer, Adam L.; Knopman, David S.; Kaufer, Daniel I.; Grossman, Murray; Onyike, Chiadikaobi U; Graf-Radford, Neill; Mendez, Mario; Kerwin, Diana; Lerner, Alan; Wu, Chuang Kuo; Koestler, Mary; Shapira, Jill; Sullivan, Kathryn; Klepac, Kristen; Lipowski, Kristine; Ullah, Jerin; Fields, Scott; Kramer, Joel H.; Merrilees, Jennifer; Neuhaus, John; Mesulam, M. Marsel; Miller, Bruce L.

In: The Lancet Neurology, Vol. 12, No. 2, 02.2013, p. 149-156.

Research output: Contribution to journalArticle

Boxer, AL, Knopman, DS, Kaufer, DI, Grossman, M, Onyike, CU, Graf-Radford, N, Mendez, M, Kerwin, D, Lerner, A, Wu, CK, Koestler, M, Shapira, J, Sullivan, K, Klepac, K, Lipowski, K, Ullah, J, Fields, S, Kramer, JH, Merrilees, J, Neuhaus, J, Mesulam, MM & Miller, BL 2013, 'Memantine in patients with frontotemporal lobar degeneration: A multicentre, randomised, double-blind, placebo-controlled trial', The Lancet Neurology, vol. 12, no. 2, pp. 149-156. https://doi.org/10.1016/S1474-4422(12)70320-4
Boxer, Adam L. ; Knopman, David S. ; Kaufer, Daniel I. ; Grossman, Murray ; Onyike, Chiadikaobi U ; Graf-Radford, Neill ; Mendez, Mario ; Kerwin, Diana ; Lerner, Alan ; Wu, Chuang Kuo ; Koestler, Mary ; Shapira, Jill ; Sullivan, Kathryn ; Klepac, Kristen ; Lipowski, Kristine ; Ullah, Jerin ; Fields, Scott ; Kramer, Joel H. ; Merrilees, Jennifer ; Neuhaus, John ; Mesulam, M. Marsel ; Miller, Bruce L. / Memantine in patients with frontotemporal lobar degeneration : A multicentre, randomised, double-blind, placebo-controlled trial. In: The Lancet Neurology. 2013 ; Vol. 12, No. 2. pp. 149-156.
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AU - Kaufer, Daniel I.

AU - Grossman, Murray

AU - Onyike, Chiadikaobi U

AU - Graf-Radford, Neill

AU - Mendez, Mario

AU - Kerwin, Diana

AU - Lerner, Alan

AU - Wu, Chuang Kuo

AU - Koestler, Mary

AU - Shapira, Jill

AU - Sullivan, Kathryn

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AU - Ullah, Jerin

AU - Fields, Scott

AU - Kramer, Joel H.

AU - Merrilees, Jennifer

AU - Neuhaus, John

AU - Mesulam, M. Marsel

AU - Miller, Bruce L.

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N2 - Background: Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26-week open-label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the neuropsychiatric inventory (NPI). We aimed to determine whether memantine is an effective treatment for FTD. Methods: We did a randomised, parallel group, double-blind, placebo-controlled trial of 20 mg memantine taken orally daily for 26 weeks in patients with FTD. Participants met Neary criteria for behavioural variant FTD (bvFTD) or semantic dementia and had characteristic brain atrophy. Use of acetylcholinesterase inhibitors was prohibited. Individuals were randomly assigned to receive either memantine or matched placebo tablets (1:1) in blocks of two and four patients. All patients and study personnel were masked to treatment assignment. Primary endpoints were the change in total NPI score and clinical global impression of change (CGIC) score after 26 weeks and were analysed by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00545974. Findings: Of 100 patients screened, 81 were randomly assigned to receive memantine (39 patients) or placebo (42 patients). Five (6%) patients discontinued, and 76 completed the 26-week treatment. Enrolment numbers were lower than planned because of many patients' preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. Memantine treatment had no effect on either the NPI (mean difference 2·2, 95% CI -3·9 to 8·3, p=0·47) or CGIC (mean difference 0·0, -0·4 to 0·4, p=0·90) after 26 weeks of treatment. Memantine was generally well tolerated; however, patients in the memantine group had more frequent cognitive adverse events (six patients) than those in the placebo group (one). Interpretation: Memantine treatment showed no benefit in patients with FTD. These data do not support memantine use in FTD. Funding: Forest Research Institute.

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